Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of human monocytes with LPS induces coordinate expression of a number of cytokine genes, including IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, and IL-8. The T cell-derived lymphokine, IL-4, inhibits expression of these genes in monocytes, suggesting that it may be an important physiologic regulator of cytokine production. We have previously shown that IL-4 reduces steady state messenger RNA (mRNA) levels for IL-1 beta in human monocytes by decreasing both IL-1 beta transcription and the t1/2 of newly formed IL-1 beta mRNA transcripts. In the present study, we extend these findings to show that IL-4 similarly accelerates the turnover of IL-6 mRNA in LPS-stimulated monocytes. However, this inhibition of cytokine expression and dramatic increase in the decay rate of cytokine mRNA does not extend to all LPS-inducible genes because IL-4 treatment did not inhibit the expression or accelerate the turnover of mRNA for the IL-1 receptor antagonist (IL-1ra) in the same cells. Although IL-1 beta and IL-1Ra are both LPS-inducible genes, they displayed distinct temporal patterns of expression. Peak steady state mRNA levels for IL-1ra lagged significantly behind that of IL-1 beta, suggesting a possible endogenous mechanism for limiting IL-1 biologic activity. Furthermore, although IL-4 suppressed expression of both IL-1 beta and IL-6, it up-regulated synthesis of IL-1ra mRNA and protein. Thus, IL-4 inhibits production of the proinflammatory cytokine, IL-1 beta, while concomitantly enhancing synthesis of the IL-1ra in activated human monocytes.
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PMID:IL-4 reciprocally regulates IL-1 and IL-1 receptor antagonist expression in human monocytes. 138 62

Expression of lymphokine genes in the human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and fresh brain specimens by PCR. mRNA transcripts for IL-8 were detected in all neuroglial cells. In addition to the cultured cells, we examined IL-8 gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The result shows that tumor and cells of the surrounding reactive lesion express IL-8 genes, but it is not expressed in normal brains. Next, the concentration of IL-8 in supernatants of cultured cells was measured quantitatively by a solid phase ELISA assay. IL-8 activity was produced constitutively in all astrocytomas and increased markedly upon stimulation with IL-1 beta or TNF alpha, in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived IL-8 may take part in neutrophil-mediated inflammation which accompanies infection, degeneration and malignancy in the brain.
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PMID:Neoplastic and reactive human astrocytes express interleukin-8 gene. 140 9

As a preliminary to transducing human melanoma cells with lymphokine genes, we sought for constitutive gene expression and production of eight interleukins, tumour necrosis factors and granulocyte-colony stimulating factor in 19 human melanoma cell lines. Conversion of RNA into cDNA by reverse transcriptase and polymerase chain reaction (RT-PCR) were employed to evaluate gene expression while enzyme-linked immunosorbent assays (ELISA) or biological assays were used to assess the presence of proteins. No expression of interleukins (IL) 3, 4, and 5 or interferon-gamma RNA was found, while the other cytokines were variably expressed in melanoma lines, with IL-1 alpha, IL-1 beta, IL-6, IL-8, being detectable in most of the lines. At protein level, 10 melanoma cells were tested with ELISA and all were found to produce IL-8, five produced IL-6, two tumour necrosis factor (TNF)-alpha, one IL-1 alpha and two TNF beta. The levels of TNF beta were at the limit of test sensitivity. The amount of various cytokines released by the different lines varied widely. Biological assay with the D10-G4 clone confirmed the presence of IL-1 alpha in the supernatant of melanoma (ME) 10221 and revealed an IL-1 activity in the supernatant of Me 4024/1. The proliferating activity of melanoma supernatants on D10-G4 was inhibited by treatment with polyclonal antibodies against IL-1 alpha but not with antibodies against IL-1 beta. TNF biological activity was tested against the TNF-susceptible fibrosarcoma WEHI 164 clone 13.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of cytokine genes, including IL-6, in human malignant melanoma cell lines. 145 Jun 72

Expression of the lymphokine genes in human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell line and 4 fresh brain specimens by polymerase chain reaction (PCR). mRNA transcripts of neither IL-1 nor IL-3, the biological activities of which were observed in rat primary cultured astrocytes, could be detected within these cell lines. Two out of 5 unstimulated astrocytomas, U138 and U373, expressed IL-6 genes. IL-8 gene was detected within U87, U138, U251, U373 glioma cells. After stimulation with IL-1 beta, all astrocytoma and one neuroblastoma cell line expressed IL-6 and IL-8 genes. In addition to the cultured cells, we examined IL-6 and IL-8 gene expression within human malignant astrocytoma specimens. The result shows that three out of four glioma specimens expressed IL-6 and IL-8 genes. From these results, it is suspected that astroglial cell-derived IL-6 or IL-8 may participate in local immune reactions accompanying infection, degeneration and malignancies in the central nervous system.
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PMID:[An analysis of lymphokine gene expression within astrocytoma]. 163 May 67

In order to identify novel mediators synthesized in activated macrophages, a cDNA library was prepared from cultures of the mouse macrophage cell line RAW 264.7 that had been treated with lymphokine-rich conditioned medium from mitogen-stimulated mouse spleen cells. Differential plaque hybridization identified a cDNA, designated m119, that detected a 1.6-kilobase mRNA that accumulated in response to gamma-interferon (IFN-gamma) but not in response to other macrophage activators, including IFN-alpha, IFN-beta, and lipopolysaccharide. The mRNA encoded a predicted protein of Mr 14,461 containing a 21-amino acid signal peptide. The primary structure of the predicted protein indicated that it is a member of a recently described family of cytokines related to platelet factor 4, including Gro/melanoma growth stimulatory activity and neutrophil-activating peptide/interleukin 8. The selective induction of the m119 mRNA by IFN-gamma that the predicted m119 protein mediates a macrophage activity regulated by IFN-gamma. The m119 protein may be a cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory responses. It is proposed that the gene encoding this protein be called mig, for monokine induced by gamma interferon.
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PMID:A macrophage mRNA selectively induced by gamma-interferon encodes a member of the platelet factor 4 family of cytokines. 211 67

Current studies on IgE-dependent allergic reactions focus on the regulation of IgE synthesis by cellular IgE receptors or by their fragments, so-called IgE-binding factors. Recent studies suggest that lymphokines, such as interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), may be more relevant in the modulation of IgE synthesis. Under this aspect studies should concentrate on the role of anti-isotypical anti-IgE antibodies which can be found frequently in IgE-mediated responses. Further studies have given new insights in the variation of releasability and lymphokine-mediated conditioning of effector cells, depending on the type of allergic reaction. Pretreatment of neutrophils with granulocyte macrophage- colony stimulating factor (GM-CSF), or basophils with interleukin-3 (IL-3) renders these cells capable of producing or releasing inflammatory mediators, such as histamine, leukotrienes or platelet activating-factor (PAF). The fact that the interaction of purified lymphokines, such as IL-3 or IL-8 with basophils causes the release of mediators, indicates a possible mechanism for the induction of immediate and delayed allergic reactions. New insights in these mechanisms may offer new immunopharmacological aspects in the treatment of allergic reactions. IgE-mediated allergic reactions can be divided into two distinct phases. During the period of sensitization allergen exposure causes the production of class E immunoglobulins (IgE) in genetically predisposed persons. Repeated allergen exposure in sensitized persons leads to bridging of IgE molecules with basophils or mast cell membranes which finally causes the production and the release of inflammation mediators, such as histamine, leukotrienes and PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New perspectives in the modulation of allergic inflammation]. 213 73

The human interleukin-3 (IL-3) receptor is constitutively expressed on certain hematopoietic cells where it mediates proliferation and differentiation, or functional activation. We have recently found that human umbilical vein endothelial cells (HUVECs) also express IL-3 receptors and that the expression is enhanced by stimulation with the monokine tumor necrosis factor alpha. In this report we show that the lymphokine interferon gamma (IFN gamma) is a powerful stimulator of the IL-3 receptor of HUVECs and that the combination of IL-3 and IFN gamma has a synergistic effect on major histocompatibility complex (MHC) class II expression and on the production of the early-acting hematopoietic cytokines IL-6 and granulocyte colony-stimulating factor (G-CSF). IFN gamma caused a time- and dose-dependent up-regulation of mRNA for both the alpha and beta chains of the IL-3 receptor, with maximal effects occurring 12 to 24 hours after stimulation with IFN gamma at 100 U/mL. Induction of mRNA correlated with protein expression on the cell surface, as judged by monoclonal antibody staining of both receptor chains and by the ability of HUVEC to specifically bind 125I-labeled IL-3 (125I-IL-3). Scatchard analysis of HUVECs stimulated with IFN gamma at 100 U/mL for 24 hours showed approximately 6,300 IL-3 receptors per cell that were of a high affinity class (dissociation constant [kd] = 500 pmol/L) only. The addition of IL-3 to IFN gamma-treated HUVECs strongly enhanced the expression of MHC class II antigen. Importantly, IFN gamma and IL-3 also exhibited a synergistic effect in the induction of the mRNA for G-CSF and IL-6. This was reflected in increased amounts of G-CSF and IL-6 protein in HUVEC supernatants. In contrast, IFN gamma and IL-3 did not stimulate granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-8 production in HUVECs. These results show that IFN gamma is a strong stimulator of IL-3 receptor expression in HUVECs and suggest that in vivo T-cell activation, causing the concomitant production of IFN gamma and IL-3, may lead to enhanced endothelial MHC class II expression and to the selective production of early-acting hematopoietic cytokines. Thus, IL-3 could influence immunity and hematopoiesis by acting not only on hematopoietic cells, but also on vascular endothelium.
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PMID:Interferon-gamma upregulates interleukin-3 (IL-3) receptor expression in human endothelial cells and synergizes with IL-3 in stimulating major histocompatibility complex class II expression and cytokine production. 754 Aug 83

The present study was undertaken to assess the effects of interleukin-1 beta (IL-1 beta) and interleukin-2 (IL-2) on glial and neuronal cells in culture. The presence of IL-1 beta-like and IL-2-like immunoreactivity was detected in media collected from both astroglial and microglial cultures, indicating that both lymphokines can be released from either cell type. However, the levels measured in microglial media were significantly higher than in the astroglial media. Moreover, the content of IL-1 beta-like immunoreactive material in the media was approximately five-to 10-fold greater than that of IL-2, although exposure of both microglial and astroglial cultures to IL-1 beta significantly enhanced this measure. A possible role for this glial-derived IL-1 beta as an astroglial growth factor was substantiated by experiments showing that the lymphokine increased the incorporation of [3H]thymidine into astroglial, but not microglial cultures. In contrast, IL-2 did not significantly alter glial proliferation. In hippocampal neuronal cultures, these lymphokines affected neuronal survival differently. Thus, only the highest concentration (500 ng/ml) of IL-1 beta tested decreased the long-term (three day), but not the short-term (one day), survival of these neurons, whereas neuronal survival was compromised by IL-2 even after short-term (one day) exposure. In addition, in the long-term (three-day-old) neuronal cultures exposed to IL-2, extensive cellular swelling, vacuolations and neurite retractions were noted, even in cultures exposed to relatively low concentrations (< 10 ng/ml) of the lymphokine. These effects were not apparent with IL-1 beta or the other lymphokines tested, including IL-3, IL-4 and IL-8. The results suggest that the glial-derived lymphokines IL-1 beta and IL-2 may have different functions in the CNS. Whereas IL-1 beta may have an important role in the developing brain as a maintenance and growth-promoting factor, IL-2 may function as an inhibitory factor, and may be of significance only in instances during which it accumulates in sufficiently high concentrations in the vicinity of neurons.
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PMID:Differential effects of interleukin-1 beta and interleukin-2 on glia and hippocampal neurons in culture. 757 76

The aim of this study was to determine whether products of enteric bacteria are able to regulate lymphocyte activation and cytokine production. Whole bacteria and bacterial lysates from different strains of Escherichia coli were tested for their ability to inhibit cytokine production by peripheral blood mononuclear cells as determined by reverse transcription-PCR, Northern (RNA) blotting of cellular RNA, or enzyme-linked immunosorbent assay for cytokine protein. Lysates from two pathogenic strains of E. coli, enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli, inhibited mitogen-stimulated expression of interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon. IL-1 beta, IL-6, IL-8, IL-10, IL-12, and Rantes mRNA expression was not affected. The inhibitory activity was dose dependent, protease and heat sensitive, nondialyzable, and not due to cellular toxicity. The inhibitory activity remained in EPEC strains having mutations in known virulence factors. Nonpathogenic E. coli HB101 transformed with a 22-kb cosmid clone derived from EPEC chromosomal DNA expressed the inhibitory activity. Thus, certain strains of pathogenic E. coli express a protein or proteins encoded by chromosomal genes that selectively inhibit lymphocyte activation and lymphokine production. Therefore, immunosuppressive factors produced by pathogenic bacteria could be important in modifying gastrointestinal immune responses in enteric bacterial infections or gastrointestinal autoimmune diseases.
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PMID:Products of enteropathogenic Escherichia coli inhibit lymphocyte activation and lymphokine production. 776 5

Human autologous tumor-specific T-helper 2 (Th2) cells were investigated in melanoma tumor-infiltrating lymphocytes (TILs). Both a CD4+ T-cell line and its 5 potential T-cell clones established from TILs of a patient with metastatic melanoma produced significant levels of IL-4, IL-6, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in response to autologous, but not any of 12 allogeneic, melanoma cell lines. They also produced IL-3 and IL-8 but not IL-2, IFN-gamma, TNF-alpha or TNF-beta in response to autologous tumor cells. Furthermore, they showed autologous melanoma-specific cytotoxicity only in an 18-hr 51Cr-release assay. Specific IL-4, IL-6 or IL-10 production by the CD4+ M73 T-cell line and its clone was inhibited by anti-class II DR (but not anti-class I) MAb, whereas their specific cytotoxicity was inhibited by anti-class I (but not anti-class II) MAb. Anti-CD3 and -CD4 MAb (but not anti-CD8) abrogated both IL-4, IL6 and IL-10 production and cytotoxicity, while anti-IL-4 antibody did not inhibit cytotoxicity. CD4+ potential T-cell clones, but not CD8+ clones, that were established from freshly isolated TILs without in vitro sensitization by autologous tumor cells also produced IL-4, IL-6 and IL-10 but not IFN-gamma or tumor necrosis factor (TNF) alpha in an autologous tumor-specific fashion. These Th2 cells were neither reactive to EBV-B cells nor suppressive against CD8+ T-cell clones. PMA and PHA stimulated these potential T-cell clones, regardless of their specific lymphokine production, to produce IL-3, IL-4, IL-6, IL-8, IL-10, GM-CSF, TNF alpha and IFN-gamma. Our results demonstrate the presence of autologous tumor-specific Th2 cells at the melanoma sites.
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PMID:Characterization of autologous tumor-specific T-helper 2 cells in tumor-infiltrating lymphocytes from a patient with metastatic melanoma. 791 81


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